ω3-Polyunsaturated fatty acids for heart failure: Effects of dose on efficacy and novel signaling through free fatty acid receptor 4

Journal of Molecular and Cellular Cardiology

Volumn 103, Issue , 2017, Pages 74-92

  O'Connell, Timothy D ^a   Block, Robert C ^b   Huang, Shue P ^c   Shearer, Gregory C ^c  

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF ROCHESTER   (United States)

^c PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

Cardiac fibrosis; Eicosapentaenoic acid (EPA); Free fatty acid receptor 4 (Ffar4); GPR120; Heart failure with preserved ejection fraction (HFpEF); Microvascular rarefaction

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; DOCOSAHEXAENOIC ACID; ENKEPHALINASE INHIBITOR; FREE FATTY ACID RECEPTOR 4; G PROTEIN COUPLED RECEPTOR; ICOSAPENTAENOIC ACID; OMEGA 3 ACID ETHYL ESTER; OMEGA 3 FATTY ACID; PHOSPHODIESTERASE INHIBITOR; PLACEBO; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; UNCLASSIFIED DRUG; CARDIOTONIC AGENT; O3FAR1 PROTEIN, HUMAN;

ACUTE HEART INFARCTION; CARDIOVASCULAR DISEASE; CHEMOPROPHYLAXIS; CONGESTIVE HEART FAILURE; DIASTOLIC DYSFUNCTION; DIET SUPPLEMENTATION; DOSE RESPONSE; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; HEART FAILURE; HEART FAILURE WITH PRESERVED EJECTION FRACTION; HEART MUSCLE FIBROSIS; HEART PROTECTION; HEART VENTRICLE REMODELING; HUMAN; ISCHEMIC HEART DISEASE; NONHUMAN; NUTRITIONAL COUNSELING; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; CLINICAL TRIAL (TOPIC); DIETARY SUPPLEMENT; DISEASE MODEL; DRUG EFFECTS; FIBROSIS; LIPID METABOLISM; METABOLISM; MOLECULARLY TARGETED THERAPY;

ANIMALS; CARDIOTONIC AGENTS; CLINICAL TRIALS AS TOPIC; DIETARY SUPPLEMENTS; DISEASE MODELS, ANIMAL; FATTY ACIDS, OMEGA-3; FIBROSIS; HEART FAILURE; HUMANS; LIPID METABOLISM; MOLECULAR TARGETED THERAPY; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION; VENTRICULAR REMODELING;

EID: 85010749610     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2016.12.003     Document Type: Review

References (125)

1. [1] Mozaffarian, D., Benjamin, E.J., Go, A.S., Arnett, D.K., Blaha, M.J., Cushman, M., et al. Executive summary: heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation 133 (2016), 447–454.
2. [2] De Caterina, R., n-3 fatty acids in cardiovascular disease. N. Engl. J. Med. 364 (2011), 2439–2450.
3. [3] Mozaffarian, D., Wu, J.H., Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J. Am. Coll. Cardiol. 58 (2011), 2047–2067.
4. [4] Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico. Lancet, 354, 1999, 447–455.
5. [5] Macchia, A., Levantesi, G., Franzosi, M.G., Geraci, E., Maggioni, A.P., Marfisi, R., et al. Left ventricular systolic dysfunction, total mortality, and sudden death in patients with myocardial infarction treated with n-3 polyunsaturated fatty acids. Eur. J. Heart Fail. 7 (2005), 904–909.
6. [6] Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di Gregorio, D., Di Mascio, R., et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 105 (2002), 1897–1903.
7. [7] Burr, M.L., Fehily, A.M., Gilbert, J.F., Rogers, S., Holliday, R.M., Sweetnam, P.M., et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 2 (1989), 757–761.
8. [8] Mozaffarian, D., Lemaitre, R.N., King, I.B., Song, X., Spiegelman, D., Sacks, F.M., et al. Circulating long-chain omega-3 fatty acids and incidence of congestive heart failure in older adults: the cardiovascular health study: a cohort study. Ann. Intern. Med. 155 (2011), 160–170.
9. [9] Tavazzi, L., Maggioni, A.P., Marchioli, R., Barlera, S., Franzosi, M.G., Latini, R., et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 372 (2008), 1223–1230.
10. [10] Nodari, S., Triggiani, M., Campia, U., Manerba, A., Milesi, G., Cesana, B.M., et al. Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J. Am. Coll. Cardiol. 57 (2011), 870–879.
11. [11] Chrysohoou, C., Metallinos, G., Georgiopoulos, G., Mendrinos, D., Papanikolaou, A., Magkas, N., et al. Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; a randomized clinical trial. Vasc. Pharmacol. 79 (2016), 43–50.
12. [12] Kohashi, K., Nakagomi, A., Saiki, Y., Morisawa, T., Kosugi, M., Kusama, Y., et al. Effects of eicosapentaenoic acid on the levels of inflammatory markers, cardiac function and long-term prognosis in chronic heart failure patients with dyslipidemia. J. Atheroscler. Thromb. 21 (2014), 712–729.
13. [13] Moertl, D., Hammer, A., Steiner, S., Hutuleac, R., Vonbank, K., Berger, R., Dose-dependent effects of omega-3-polyunsaturated fatty acids on systolic left ventricular function, endothelial function, and markers of inflammation in chronic heart failure of nonischemic origin: a double-blind, placebo-controlled, 3-arm study. Am. Heart J., 161, 2011 (915 e1-9).
14. [14] Brownawell, A.M., Harris, W.S., Hibbeln, J.R., Klurfeld, D.M., Newton, I., Yates, A., Assessing the environment for regulatory change for eicosapentaenoic acid and docosahexaenoic acid nutrition labeling. Nutr. Rev. 67 (2009), 391–397.
15. 2 +-induced permeability transition. J. Mol. Cell. Cardiol. 47 (2009), 819–827.
16. [16] Galvao, T.F., Khairallah, R.J., Dabkowski, E.R., Brown, B.H., Hecker, P.A., O'Connell, K.A., et al. Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival. Am. J. Physiol. Heart Circ. Physiol. 304 (2013), H12–H21.
17. [17] Dabkowski, E.R., O'Connell, K.A., Xu, W., Ribeiro, R.F. Jr., Hecker, P.A., Shekar, K.C., et al. Docosahexaenoic acid supplementation alters key properties of cardiac mitochondria and modestly attenuates development of left ventricular dysfunction in pressure overload-induced heart failure. Cardiovasc. Drugs Ther. 27 (2013), 499–510.
18. [18] McLennan, P.L., Abeywardena, M.Y., Dallimore, J.A., Raederstorff, D., Dietary fish oil preserves cardiac function in the hypertrophied rat heart. Br. J. Nutr. 108 (2012), 645–654.
19. [19] Yamanushi, T.T., Kabuto, H., Hirakawa, E., Janjua, N., Takayama, F., Mankura, M., Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats. J. Nutr. 144 (2014), 467–474.
20. [20] Chen, J., Shearer, G.C., Chen, Q., Healy, C.L., Beyer, A.J., Nareddy, V.B., et al. Omega-3 fatty acids prevent pressure overload-induced cardiac fibrosis through activation of cyclic GMP/protein kinase G signaling in cardiac fibroblasts. Circulation 123 (2011), 584–593.
21. [21] Eclov, J.A., Qian, Q., Redetzke, R., Chen, Q., Wu, S.C., Healy, C.L., et al. EPA, not DHA, prevents fibrosis in pressure overload induced heart failure; potential role of free fatty acid receptor 4. J. Lipid Res. 56 (2015), 2297–2308.
22. [22] Heydari, B., Abdullah, S., Pottala, J.V., Shah, R., Abbasi, S., Mandry, D., et al. Effect of omega-3 acid ethyl esters on left ventricular remodeling after acute myocardial infarction: the OMEGA-REMODEL randomized clinical trial. Circulation 134 (2016), 378–391.
23. [23] Poudyal, H., Brown, L., The role of n-3 polyunsaturated fatty acids in human heart failure. Endocr Metab Immune Disord Drug Targets 13 (2013), 105–117.
24. [24] Harris, W.S., Poston, W.C., Haddock, C.K., Tissue n-3 and n-6 fatty acids and risk for coronary heart disease events. Atherosclerosis 193 (2007), 1–10.
25. [25] Lavie, C.J., Milani, R.V., Mehra, M.R., Ventura, H.O., Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J. Am. Coll. Cardiol. 54 (2009), 585–594.
26. [26] Mozaffarian, D., Rimm, E.B., Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 296 (2006), 1885–1899.
27. [27] Harris, W.S., Mozaffarian, D., Lefevre, M., Toner, C.D., Colombo, J., Cunnane, S.C., et al. Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J. Nutr., 139, 2009 (804S-19S).
28. [28] He, K., Song, Y., Daviglus, M.L., Liu, K., Van Horn, L., Dyer, A.R., et al. Accumulated evidence on fish consumption and coronary heart disease mortality: a meta-analysis of cohort studies. Circulation 109 (2004), 2705–2711.
29. [29] Leon, H., Shibata, M.C., Sivakumaran, S., Dorgan, M., Chatterley, T., Tsuyuki, R.T., Effect of fish oil on arrhythmias and mortality: systematic review. BMJ, 337, 2008, a2931.
30. [30] Marik, P.E., Varon, J., Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin. Cardiol. 32 (2009), 365–372.
31. [31] Del Gobbo, L.C., Imamura, F., Aslibekyan, S., Marklund, M., Virtanen, J.K., Wennberg, M., et al. Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies. JAMA Intern. Med., 2016.
32. [32] Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., Ishikawa, Y., et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369 (2007), 1090–1098.
33. [33] Burr, M.L., Ashfield-Watt, P.A., Dunstan, F.D., Fehily, A.M., Breay, P., Ashton, T., et al. Lack of benefit of dietary advice to men with angina: results of a controlled trial. Eur. J. Clin. Nutr. 57 (2003), 193–200.
34. [34] Kromhout, D., Giltay, E.J., Geleijnse, J.M., Alpha Omega Trial G, n-3 fatty acids and cardiovascular events after myocardial infarction. N. Engl. J. Med. 363 (2010), 2015–2026.
35. [35] Rauch, B., Schiele, R., Schneider, S., Diller, F., Victor, N., Gohlke, H., et al. OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation 122 (2010), 2152–2159.
36. [36] Galan, P., Kesse-Guyot, E., Czernichow, S., Briancon, S., Blacher, J., Hercberg, S., et al. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ, 341, 2010, c6273.
37. [37] Rizos, E.C., Ntzani, E.E., Bika, E., Kostapanos, M.S., Elisaf, M.S., Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA 308 (2012), 1024–1033.
38. [38] Galli, C., Brenna, J.T., Omega-3 fatty acid supplementation and cardiovascular disease events. JAMA 309 (2013), 28–29.
39. [39] Lewis, E.J., Omega-3 fatty acid supplementation and cardiovascular disease events. JAMA, 309, 2013, 27.
40. [40] Sethi, A., Singh, M., Arora, R., Omega-3 fatty acid supplementation and cardiovascular disease events. JAMA 309 (2013), 27–28.
41. [41] Vlachopoulos, C., Richter, D., Stefanadis, C., Omega-3 fatty acid supplementation and cardiovascular disease events. JAMA, 309, 2013, 28.
42. [42] Chowdhury, R., Warnakula, S., Kunutsor, S., Crowe, F., Ward, H.A., Johnson, L., et al. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann. Intern. Med. 160 (2014), 398–406.
43. [43] Superko, H.R., Superko, S.M., Nasir, K., Agatston, A., Garrett, B.C., Omega-3 fatty acid blood levels: clinical significance and controversy. Circulation 128 (2013), 2154–2161.
44. [44] Donadio, J.V., Bergstralh, E.J., Bibus, D.M., Grande, J.P., Is body size a biomarker for optimizing dosing of omega-3 polyunsaturated fatty acids in the treatment of patients with IgA nephropathy?. Clin. J. Am. Soc. Nephrol. 1 (2006), 933–939.
45. [45] Donadio, J.V. Jr., Larson, T.S., Bergstralh, E.J., Grande, J.P., A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy. J. Am. Soc. Nephrol. 12 (2001), 791–799.
46. [46] Laidlaw, M., Holub, B.J., Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am. J. Clin. Nutr. 77 (2003), 37–42.
47. [47] Flock, M.R., Skulas-Ray, A.C., Harris, W.S., Etherton, T.D., Fleming, J.A., Kris-Etherton, P.M., Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial. J. Am. Heart Assoc., 2, 2013, e000513.
48. [48] Sacks, F.M., Stone, P.H., Gibson, C.M., Silverman, D.I., Rosner, B., Pasternak, R.C., Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J. Am. Coll. Cardiol. 25 (1995), 1492–1498.
49. [49] von Schacky, C., Angerer, P., Kothny, W., Theisen, K., Mudra, H., The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 130 (1999), 554–562.
50. [50] Raitt, M.H., Connor, W.E., Morris, C., Kron, J., Halperin, B., Chugh, S.S., et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 293 (2005), 2884–2891.
51. [51] Brouwer, I.A., Zock, P.L., Camm, A.J., Bocker, D., Hauer, R.N., Wever, E.F., et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 295 (2006), 2613–2619.
52. [52] Leaf, A., Albert, C.M., Josephson, M., Steinhaus, D., Kluger, J., Kang, J.X., et al. Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Circulation 112 (2005), 2762–2768.
53. [53] Einvik, G., KLemsdal, T.O., Sandvik, L., Hjerkinn, E.M., A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk. Eur. J. Cardiovasc. Prev. Rehabil. 17 (2010), 588–592.
54. [54] Nilsen, D.W., Albrektsen, G., Landmark, K., Moen, S., Aarsland, T., Woie, L., Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Am. J. Clin. Nutr. 74 (2001), 50–56.
55. [55] Origin Trial Investigators, Bosch, J., Gerstein, H.C., Dagenais, G.R., Diaz, R., Dyal, L., et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N. Engl. J. Med. 367 (2012), 309–318.
56. [56] Risk, Prevention Study Collaborative Group. n-3 fatty acids in patients with multiple cardiovascular risk factors. N. Engl. J. Med., 368, 2013, 1800–1808.
57. [57] Eritsland, J., Arnesen, H., Gronseth, K., Fjeld, N.B., Abdelnoor, M., Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am. J. Cardiol. 77 (1996), 31–36.
58. [58] Stark, K.D., Van Elswyk, M.E., Higgins, M.R., Weatherford, C.A., Salem, N. Jr., Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog. Lipid Res. 63 (2016), 132–152.
59. [59] Augustine, A.H., Lowenstein, L.M., Harris, W.S., Shearer, G.C., Block, R.C., Treatment with omega-3 fatty acid ethyl-ester alters fatty acid composition of lipoproteins in overweight or obese adults with insulin resistance. Prostaglandins Leukot. Essent. Fat. Acids 90 (2014), 69–75.
60. [60] Braeckman, R.A., Manku, M.S., Bays, H.E., Stirtan, W.G., Soni, P.N., Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on plasma and red blood cell fatty acids in patients with very high triglyceride levels (results from the MARINE study). Prostaglandins Leukot. Essent. Fat. Acids 89 (2013), 195–201.
61. [61] Tazoe, H., Otomo, Y., Kaji, I., Tanaka, R., Karaki, S.I., Kuwahara, A., Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J. Physiol. Pharmacol. 59:Suppl. 2 (2008), 251–262.
62. [62] Wang, J., Wu, X., Simonavicius, N., Tian, H., Ling, L., Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J. Biol. Chem. 281 (2006), 34457–34464.
63. [63] Hirasawa, A., Tsumaya, K., Awaji, T., Katsuma, S., Adachi, T., Yamada, M., et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat. Med. 11 (2005), 90–94.
64. [64] Itoh, Y., Kawamata, Y., Harada, M., Kobayashi, M., Fujii, R., Fukusumi, S., et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422 (2003), 173–176.
65. [65] Tanaka, T., Yano, T., Adachi, T., Koshimizu, T.A., Hirasawa, A., Tsujimoto, G., Cloning and characterization of the rat free fatty acid receptor GPR120: in vivo effect of the natural ligand on GLP-1 secretion and proliferation of pancreatic beta cells. Naunyn Schmiedeberg's Arch. Pharmacol. 377 (2008), 515–522.
66. [66] Cornall, L.M., Mathai, M.L., Hryciw, D.H., McAinch, A.J., Diet-induced obesity up-regulates the abundance of GPR43 and GPR120 in a tissue specific manner. Cell. Physiol. Biochem. 28 (2011), 949–958.
67. [67] Oh, D.Y., Talukdar, S., Bae, E.J., Imamura, T., Morinaga, H., Fan, W., et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142 (2010), 687–698.
68. [68] Cornall, L.M., Mathai, M.L., Hryciw, D.H., AJ, M.A., GPR120 agonism as a countermeasure against metabolic diseases. Drug Discov. Today 19 (2014), 670–679.
69. [69] Burns, R.N., Moniri, N.H., Agonism with the omega-3 fatty acids alpha-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor. Biochem. Biophys. Res. Commun. 396 (2010), 1030–1035.
70. [70] Watson, S.J., Brown, A.J., Holliday, N.D., Differential signaling by splice variants of the human free fatty acid receptor GPR120. Mol. Pharmacol. 81 (2012), 631–642.
71. [71] Galindo, M.M., Voigt, N., Stein, J., van Lengerich, J., Raguse, J.D., Hofmann, T., et al. G protein-coupled receptors in human fat taste perception. Chem. Senses 37 (2012), 123–139.
72. [72] Milligan, G., Alvarez-Curto, E., Watterson, K.R., Ulven, T., Hudson, B.D., Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4. Br. J. Pharmacol. 172 (2015), 3254–3265.
73. [73] Shaikh, S.R., Biophysical and biochemical mechanisms by which dietary N-3 polyunsaturated fatty acids from fish oil disrupt membrane lipid rafts. J. Nutr. Biochem. 23 (2012), 101–105.
74. [74] Chapkin, R.S., McMurray, D.N., Davidson, L.A., Patil, B.S., Fan, Y.Y., Lupton, J.R., Bioactive dietary long-chain fatty acids: emerging mechanisms of action. Br. J. Nutr. 100 (2008), 1152–1157.
75. [75] Wassall, S.R., Stillwell, W., Docosahexaenoic acid domains: the ultimate non-raft membrane domain. Chem. Phys. Lipids 153 (2008), 57–63.
76. [76] Wassall, S.R., Stillwell, W., Polyunsaturated fatty acid-cholesterol interactions: domain formation in membranes. Biochim. Biophys. Acta 1788 (2009), 24–32.
77. [77] Buxton, I.L., Duan, D., Cyclic GMP/protein kinase G phosphorylation of Smad3 blocks transforming growth factor-beta-induced nuclear Smad translocation: a key antifibrogenic mechanism of atrial natriuretic peptide. Circ. Res. 102 (2008), 151–153.
78. [78] Li, P., Wang, D., Lucas, J., Oparil, S., Xing, D., Cao, X., et al. Atrial natriuretic peptide inhibits transforming growth factor beta-induced Smad signaling and myofibroblast transformation in mouse cardiac fibroblasts. Circ. Res. 102 (2008), 185–192.
79. [79] Ritchie, R.H., Irvine, J.C., Rosenkranz, A.C., Patel, R., Wendt, I.R., Horowitz, J.D., et al. Exploiting cGMP-based therapies for the prevention of left ventricular hypertrophy: NO* and beyond. Pharmacol. Ther. 124 (2009), 279–300.
80. [80] Tsai, E.J., Kass, D.A., Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics. Pharmacol. Ther. 122 (2009), 216–238.
81. [81] Harris, W.S., Rambjor, G.S., Windsor, S.L., Diederich, D., n-3 fatty acids and urinary excretion of nitric oxide metabolites in humans. Am. J. Clin. Nutr. 65 (1997), 459–464.
82. [82] Mohammed, S.F., Hussain, S., Mirzoyev, S.A., Edwards, W.D., Maleszewski, J.J., Redfield, M.M., Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation 131 (2015), 550–559.
83. [83] Turgeon, J., Dussault, S., Maingrette, F., Groleau, J., Haddad, P., Perez, G., et al. Fish oil-enriched diet protects against ischemia by improving angiogenesis, endothelial progenitor cell function and postnatal neovascularization. Atherosclerosis 229 (2013), 295–303.
84. [84] Hasan, A.U., Ohmori, K., Konishi, K., Igarashi, J., Hashimoto, T., Kamitori, K., et al. Eicosapentaenoic acid upregulates VEGF-A through both GPR120 and PPARgamma mediated pathways in 3T3-L1 adipocytes. Mol. Cell. Endocrinol. 406 (2015), 10–18.
85. [85] Glezeva, N., Horgan, S., Baugh, J.A., Monocyte and macrophage subsets along the continuum to heart failure: misguided heroes or targetable villains?. J. Mol. Cell. Cardiol. 89 (2015), 136–145.
86. [86] Panigrahy, D., Kalish, B.T., Huang, S., Bielenberg, D.R., Le, H.D., Yang, J., et al. Epoxyeicosanoids promote organ and tissue regeneration. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 13528–13533.
87. [87] Pozzi, A., Macias-Perez, I., Abair, T., Wei, S., Su, Y., Zent, R., et al. Characterization of 5,6- and 8,9-epoxyeicosatrienoic acids (5,6- and 8,9-EET) as potent in vivo angiogenic lipids. J. Biol. Chem. 280 (2005), 27138–27146.
88. [88] Dai, M., Wu, L., He, Z., Zhang, S., Chen, C., Xu, X., et al. Epoxyeicosatrienoic acids regulate macrophage polarization and prevent LPS-induced cardiac dysfunction. J. Cell. Physiol. 230 (2015), 2108–2119.
89. [89] Ye, D., Zhang, D., Oltman, C., Dellsperger, K., Lee, H.C., VanRollins, M., Cytochrome p-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels. J. Pharmacol. Exp. Ther. 303 (2002), 768–776.
90. [90] Morin, C., Sirois, M., Echave, V., Albadine, R., Rousseau, E., 17,18-Epoxyeicosatetraenoic acid targets PPAR gamma and p38 mitogen-activated protein kinase to mediate its anti-inflammatory effects in the lung. Am. J. Respir. Cell Mol. Biol. 43 (2010), 564–575.
91. [91] Kunisawa, J., Arita, M., Hayasaka, T., Harada, T., Iwamoto, R., Nagasawa, R., et al. Dietary omega 3 fatty acid exerts anti-allergic effect through the conversion to 17,18-epoxyeicosatetraenoic acid in the gut. Sci. Rep. U.K., 5, 2015.
92. [92] Owan, T.E., Hodge, D.O., Herges, R.M., Jacobsen, S.J., Roger, V.L., Redfield, M.M., Trends in prevalence and outcome of heart failure with preserved ejection fraction. N. Engl. J. Med. 355 (2006), 251–259.
93. [93] Borlaug, B.A., Redfield, M.M., Diastolic and systolic heart failure are distinct phenotypes within the heart failure spectrum. Circulation 123 (2011), 2006–2013 (discussion 14).
94. [94] Butler, J., Fonarow, G.C., Zile, M.R., Lam, C.S., Roessig, L., Schelbert, E.B., et al. Developing therapies for heart failure with preserved ejection fraction: current state and future directions. JACC Heart Fail. 2 (2014), 97–112.
95. [95] Steinberg, B.A., Zhao, X., Heidenreich, P.A., Peterson, E.D., Bhatt, D.L., Cannon, C.P., et al. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation 126 (2012), 65–75.
96. [96] Fonarow, G.C., Stough, W.G., Abraham, W.T., Albert, N.M., Gheorghiade, M., Greenberg, B.H., et al. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF Registry. J. Am. Coll. Cardiol. 50 (2007), 768–777.
97. [97] Massie, B.M., Carson, P.E., McMurray, J.J., Komajda, M., McKelvie, R., Zile, M.R., et al. Irbesartan in patients with heart failure and preserved ejection fraction. N. Engl. J. Med. 359 (2008), 2456–2467.
98. [98] Yusuf, S., Pfeffer, M.A., Swedberg, K., Granger, C.B., Held, P., McMurray, J.J., et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 362 (2003), 777–781.
99. [99] Solomon, S.D., Zile, M., Pieske, B., Voors, A., Shah, A., Kraigher-Krainer, E., et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet 380 (2012), 1387–1395.
100. [100] Redfield, M.M., Chen, H.H., Borlaug, B.A., Semigran, M.J., Lee, K.L., Lewis, G., et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. JAMA 309 (2013), 1268–1277.
101. [101] Edelmann, F., Wachter, R., Schmidt, A.G., Kraigher-Krainer, E., Colantonio, C., Kamke, W., et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. JAMA 309 (2013), 781–791.
102. [102] Desai, A.S., Lewis, E.F., Li, R., Solomon, S.D., Assmann, S.F., Boineau, R., et al. Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am. Heart J., 162, 2011 (966-72 e10).
103. [103] Paulus, W.J., Tschope, C., Sanderson, J.E., Rusconi, C., Flachskampf, F.A., Rademakers, F.E., et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur. Heart J. 28 (2007), 2539–2550.
104. [104] Vasan, R.S., Levy, D., Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation 101 (2000), 2118–2121.
105. [105] McMurray, J.J., Adamopoulos, S., Anker, S.D., Auricchio, A., Bohm, M., Dickstein, K., et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 33 (2012), 1787–1847.
106. [106] Members of the Writing Committee, Yancy, C.W., Jessup, M., Bozkurt, B., Butler, J., Casey, D.E. Jr., et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 128 (2013), e240–e327.
107. [107] Berk, B.C., Fujiwara, K., Lehoux, S.E.C.M., Remodeling in hypertensive heart disease. J. Clin. Invest. 117 (2007), 568–575.
108. [108] van Heerebeek, L., Borbely, A., Niessen, H.W., Bronzwaer, J.G., van der Velden, J., Stienen, G.J., et al. Myocardial structure and function differ in systolic and diastolic heart failure. Circulation 113 (2006), 1966–1973.
109. [109] Zile, M.R., Brutsaert, D.L., New concepts in diastolic dysfunction and diastolic heart failure: part II: causal mechanisms and treatment. Circulation 105 (2002), 1503–1508.
110. [110] From, A.M., Borlaug, B.A., Heart failure with preserved ejection fraction: pathophysiology and emerging therapies. Cardiovasc. Ther. 29 (2010), e6–21.
111. [111] Senni, M., Paulus, W.J., Gavazzi, A., Fraser, A.G., Diez, J., Solomon, S.D., et al. New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes. Eur. Heart J. 35 (2014), 2797–2815.
112. [112] Zile, M.R., Baicu, C.F., Ikonomidis, J.S., Stroud, R.E., Nietert, P.J., Bradshaw, A.D., et al. Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin. Circulation 131 (2015), 1247–1259.
113. [113] Hinz, B., Phan, S.H., Thannickal, V.J., Prunotto, M., Desmouliere, A., Varga, J., et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am. J. Pathol. 180 (2012), 1340–1355.
114. [114] Wynn, T.A., Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J. Clin. Invest. 117 (2007), 524–529.
115. [115] Hoenig, M.R., Bianchi, C., Rosenzweig, A., Sellke, F.W., The cardiac microvasculature in hypertension, cardiac hypertrophy and diastolic heart failure. Cur. Vasc. Pharmacol. 6 (2008), 292–300.
116. [116] Paulus, W.J., Tschope, C.A., novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J. Am. Coll. Cardiol. 62 (2013), 263–271.
117. [117] Shah, S.J., Kitzman, D.W., Borlaug, B.A., van Heerebeek, L., Zile, M.R., Kass, D.A., et al. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation 134 (2016), 73–90.
118. [118] Westermann, D., Lindner, D., Kasner, M., Zietsch, C., Savvatis, K., Escher, F., et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ. Heart Fail. 4 (2011), 44–52.
119. [119] Franssen, C., Chen, S., Unger, A., Korkmaz, H.I., De Keulenaer, G.W., Tschope, C., et al. Myocardial microvascular inflammatory endothelial activation in heart failure with preserved ejection fraction. JACC Heart Fail. 4 (2016), 312–324.
120. [120] van Heerebeek, L., Hamdani, N., Falcao-Pires, I., Leite-Moreira, A.F., Begieneman, M.P., Bronzwaer, J.G., et al. Low myocardial protein kinase G activity in heart failure with preserved ejection fraction. Circulation 126 (2012), 830–839.
121. [121] Shearer, G.C., Pottala, J.V., Hansen, S.N., Brandenburg, V., Harris, W.S., Effects of prescription niacin and omega-3 fatty acids on lipids and vascular function in metabolic syndrome: a randomized controlled trial. J. Lipid Res. 53 (2012), 2429–2435.
122. [122] Horgan, S., Watson, C., Glezeva, N., Baugh, J., Murine models of diastolic dysfunction and heart failure with preserved ejection fraction. J. Card. Fail. 20 (2014), 984–995.
123. [123] Oikawa, S., Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., et al. Suppressive effect of EPA on the incidence of coronary events in hypercholesterolemia with impaired glucose metabolism: Sub-analysis of the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 206 (2009), 535–539.
124. [124] Svensson, M., Schmidt, E.B., Jorgensen, K.A., Christensen, J.H., Group, O.S., N-3 fatty acids as secondary prevention against cardiovascular events in patients who undergo chronic hemodialysis: a randomized, placebo-controlled intervention trial. Clin. J. Am. Soc. Nephrol. 1 (2006), 780–786.
125. [125] Macchia, A., Grancelli, H., Varini, S., Nul, D., Laffaye, N., Mariani, J., et al. Omega-3 fatty acids for the prevention of recurrent symptomatic atrial fibrillation: results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) trial. J. Am. Coll. Cardiol. 61 (2013), 463–468.